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1.
J Clin Med ; 10(8)2021 Apr 10.
Article in English | MEDLINE | ID: covidwho-1526832

ABSTRACT

The global emergency produced by COVID-19 has been a turning point for health organizations. Healthcare professionals have been exposed to high levels of stress and workload. Close contact with infected patients and the infectious capacity of COVID-19 mean that this group is especially vulnerable to contagion. In various countries, the Fear of COVID-19 Scale has been shown to be a fast and reliable tool. Early detection of fear complements clinical efforts to prevent emotional disorders. Thus, concepts focused on positive occupational health, such as Job Crafting or psychological empowerment (PE), have been examined as a tool to prevent mental health problems at work. In this work, we intended to adapt and validate the 7-item Fear of COVID-19 Scale in health workers (N = 194). The interpretation of the measurement model indicates adequate values of internal consistency reliability, and convergent and discriminant validity. The overall goodness of fit of the model was also adequate. The structural model indicates that the implementation of job crafting measures in health services leads to workers' greater PE. High levels of anxiety and depression prevent health professionals from psychologically detaching from work. In turn, PE can reduce the emotional disorders caused by the fear of COVID-19.

2.
J Biomol Struct Dyn ; 39(13): 4936-4948, 2021 08.
Article in English | MEDLINE | ID: covidwho-1521983

ABSTRACT

The SARS-CoV-2 was confirmed to cause the global pandemic of coronavirus disease 2019 (COVID-19). The 3-chymotrypsin-like protease (3CLpro), an essential enzyme for viral replication, is a valid target to combat SARS-CoV and MERS-CoV. In this work, we present a structure-based study to identify potential covalent inhibitors containing a variety of chemical warheads. The targeted Asinex Focused Covalent (AFCL) library was screened based on different reaction types and potential covalent inhibitors were identified. In addition, we screened FDA-approved protease inhibitors to find candidates to be repurposed against SARS-CoV-2 3CLpro. A number of compounds with significant covalent docking scores were identified. These compounds were able to establish a covalent bond (C-S) with the reactive thiol group of Cys145 and to form favorable interactions with residues lining the substrate-binding site. Moreover, paritaprevir and simeprevir from FDA-approved protease inhibitors were identified as potential inhibitors of SARS-CoV-2 3CLpro. The mechanism and dynamic stability of binding between the identified compounds and SARS-CoV-2 3CLpro were characterized by molecular dynamics (MD) simulations. The identified compounds are potential inhibitors worthy of further development as COVID-19 drugs. Importantly, the identified FDA-approved anti-hepatitis-C virus (HCV) drugs paritaprevir and simeprevir could be ready for clinical trials to treat infected patients and help curb COVID-19. Communicated by Ramaswamy H. Sarma.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Peptide Hydrolases , Protease Inhibitors/pharmacology
3.
Br J Clin Pharmacol ; 87(9): 3425-3438, 2021 09.
Article in English | MEDLINE | ID: covidwho-1494607

ABSTRACT

AIMS: We propose the use of in silico mathematical models to provide insights that optimize therapeutic interventions designed to effectively treat respiratory infection during a pandemic. A modelling and simulation framework is provided using SARS-CoV-2 as an example, considering applications for both treatment and prophylaxis. METHODS: A target cell-limited model was used to quantify the viral infection dynamics of SARS-CoV-2 in a pooled population of 105 infected patients. Parameter estimates from the resulting model were used to simulate and compare the impact of various interventions against meaningful viral load endpoints. RESULTS: Robust parameter estimates were obtained for the basic reproduction number, viral release rate and infected-cell mortality from the infection model. These estimates were informed by the largest dataset currently available for SARS-CoV-2 viral time course. The utility of this model was demonstrated using simulations, which hypothetically introduced inhibitory or stimulatory drug mechanisms at various target sites within the viral life-cycle. We show that early intervention is crucial to achieving therapeutic benefit when monotherapy is administered. In contrast, combination regimens of two or three drugs may provide improved outcomes if treatment is initiated late. The latter is relevant to SARS-CoV-2, where the period between infection and symptom onset is relatively long. CONCLUSIONS: The use of in silico models can provide viral load predictions that can rationalize therapeutic strategies against an emerging viral pathogen.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/drug therapy , Computer Simulation , Humans , Pandemics , SARS-CoV-2/drug effects , Viral Load
4.
Engineering (Beijing) ; 7(7): 958-965, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1482579

ABSTRACT

The longitudinal immunologic status of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and its association with the clinical outcome are barely known. Thus, we sought to analyze the temporal profiles of specific antibodies, as well as the associations between the antibodies, proinflammatory cytokines, and survival of patients with coronavirus disease 2019 (COVID-19). A total of 1830 laboratory-confirmed COVID-19 cases were recruited. The temporal profiles of the virus, antibodies, and cytokines of the patients until 12 weeks since illness onset were fitted by the locally weighted scatter plot smoothing method. The mediation effect of cytokines on the associations between antibody responses and survival were explored by mediation analysis. Of the 1830 patients, 1435 were detectable for SARS-CoV-2, while 395 were positive in specific antibodies only. Of the 1435 patients, 2.4% presented seroconversion for neither immunoglobulin G (IgG) nor immunoglobulin M (IgM) during hospitalization. The seropositive rates of IgG and IgM were 29.6% and 48.1%, respectively, in the first week, and plateaued within five weeks. For the patients discharged from the hospital, the IgM decreased slowly, while high levels of IgG were maintained at around 188 AU·mL-1 for the 12 weeks since illness onset. In contrast, in the patients who subsequently died, IgM declined rapidly and IgG dropped to 87 AU·mL-1 at the twelfth week. Elevated interleukin-6, interleukin-8, interleukin-10, interleukin-1ß, interleukin-2R, and tumor necrosis factor-α levels were observed in the deceased patients in comparison with the discharged patients, and 12.5% of the association between IgG level and mortality risk was mediated by these cytokines. Our study deciphers the temporal profiles of SARS-CoV-2-specific antibodies within the 12 weeks since illness onset and indicates the protective effect of antibody response on survival, which may help to guide prognosis estimation.

5.
Clin Infect Dis ; 73(7): e1878-e1880, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1455258

ABSTRACT

Many patients are fearful of acquiring coronavirus disease 2019 (COVID-19) in hospitals and clinics. We characterized the risk of COVID-19 among 226 patients exposed to healthcare workers with confirmed COVID-19. One patient may have been infected, suggesting that the risk of COVID-19 transmission from healthcare workers to patients is generally low.


Subject(s)
COVID-19 , Health Personnel , Humans , SARS-CoV-2
6.
Anaesthesist ; 69(10): 717-725, 2020 10.
Article in German | MEDLINE | ID: covidwho-1453673

ABSTRACT

BACKGROUND: Following the regional outbreak in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread all over the world, presenting the healthcare systems with huge challenges worldwide. In Germany the coronavirus diseases 2019 (COVID-19) pandemic has resulted in a slowly growing demand for health care with a sudden occurrence of regional hotspots. This leads to an unpredictable situation for many hospitals, leaving the question of how many bed resources are needed to cope with the surge of COVID-19 patients. OBJECTIVE: In this study we created a simulation-based prognostic tool that provides the management of the University Hospital of Augsburg and the civil protection services with the necessary information to plan and guide the disaster response to the ongoing pandemic. Especially the number of beds needed on isolation wards and intensive care units (ICU) are the biggest concerns. The focus should lie not only on the confirmed cases as the patients with suspected COVID-19 are in need of the same resources. MATERIAL AND METHODS: For the input we used the latest information provided by governmental institutions about the spreading of the disease, with a special focus on the growth rate of the cumulative number of cases. Due to the dynamics of the current situation, these data can be highly variable. To minimize the influence of this variance, we designed distribution functions for the parameters growth rate, length of stay in hospital and the proportion of infected people who need to be hospitalized in our area of responsibility. Using this input, we started a Monte Carlo simulation with 10,000 runs to predict the range of the number of hospital beds needed within the coming days and compared it with the available resources. RESULTS: Since 2 February 2020 a total of 306 patients were treated with suspected or confirmed COVID-19 at this university hospital. Of these 84 needed treatment on the ICU. With the help of several simulation-based forecasts, the required ICU and normal bed capacity at Augsburg University Hospital and the Augsburg ambulance service in the period from 28 March 2020 to 8 June 2020 could be predicted with a high degree of reliability. Simulations that were run before the impact of the restrictions in daily life showed that we would have run out of ICU bed capacity within approximately 1 month. CONCLUSION: Our simulation-based prognosis of the health care capacities needed helps the management of the hospital and the civil protection service to make reasonable decisions and adapt the disaster response to the realistic needs. At the same time the forecasts create the possibility to plan the strategic response days and weeks in advance. The tool presented in this study is, as far as we know, the only one accounting not only for confirmed COVID-19 cases but also for suspected COVID-19 patients. Additionally, the few input parameters used are easy to access and can be easily adapted to other healthcare systems.


Subject(s)
Coronavirus Infections/therapy , Critical Care/organization & administration , Hospital Bed Capacity , Hospitals, University/organization & administration , Intensive Care Units/organization & administration , Pneumonia, Viral/therapy , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/epidemiology , Critical Care/statistics & numerical data , Germany , Hospitals, University/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Pandemics , Pneumonia, Viral/epidemiology , Prognosis , SARS-CoV-2
7.
JAMA ; 323(16): 1574-1581, 2020 04 28.
Article in English | MEDLINE | ID: covidwho-1453471

ABSTRACT

Importance: In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Information about the clinical characteristics of infected patients who require intensive care is limited. Objective: To characterize patients with coronavirus disease 2019 (COVID-19) requiring treatment in an intensive care unit (ICU) in the Lombardy region of Italy. Design, Setting, and Participants: Retrospective case series of 1591 consecutive patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinator center (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network and treated at one of the ICUs of the 72 hospitals in this network between February 20 and March 18, 2020. Date of final follow-up was March 25, 2020. Exposures: SARS-CoV-2 infection confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs. Main Outcomes and Measures: Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Data were recorded by the coordinator center on an electronic worksheet during telephone calls by the staff of the COVID-19 Lombardy ICU Network. Results: Of the 1591 patients included in the study, the median (IQR) age was 63 (56-70) years and 1304 (82%) were male. Of the 1043 patients with available data, 709 (68%) had at least 1 comorbidity and 509 (49%) had hypertension. Among 1300 patients with available respiratory support data, 1287 (99% [95% CI, 98%-99%]) needed respiratory support, including 1150 (88% [95% CI, 87%-90%]) who received mechanical ventilation and 137 (11% [95% CI, 9%-12%]) who received noninvasive ventilation. The median positive end-expiratory pressure (PEEP) was 14 (IQR, 12-16) cm H2O, and Fio2 was greater than 50% in 89% of patients. The median Pao2/Fio2 was 160 (IQR, 114-220). The median PEEP level was not different between younger patients (n = 503 aged ≤63 years) and older patients (n = 514 aged ≥64 years) (14 [IQR, 12-15] vs 14 [IQR, 12-16] cm H2O, respectively; median difference, 0 [95% CI, 0-0]; P = .94). Median Fio2 was lower in younger patients: 60% (IQR, 50%-80%) vs 70% (IQR, 50%-80%) (median difference, -10% [95% CI, -14% to 6%]; P = .006), and median Pao2/Fio2 was higher in younger patients: 163.5 (IQR, 120-230) vs 156 (IQR, 110-205) (median difference, 7 [95% CI, -8 to 22]; P = .02). Patients with hypertension (n = 509) were older than those without hypertension (n = 526) (median [IQR] age, 66 years [60-72] vs 62 years [54-68]; P < .001) and had lower Pao2/Fio2 (median [IQR], 146 [105-214] vs 173 [120-222]; median difference, -27 [95% CI, -42 to -12]; P = .005). Among the 1581 patients with ICU disposition data available as of March 25, 2020, 920 patients (58% [95% CI, 56%-61%]) were still in the ICU, 256 (16% [95% CI, 14%-18%]) were discharged from the ICU, and 405 (26% [95% CI, 23%-28%]) had died in the ICU. Older patients (n = 786; age ≥64 years) had higher mortality than younger patients (n = 795; age ≤63 years) (36% vs 15%; difference, 21% [95% CI, 17%-26%]; P < .001). Conclusions and Relevance: In this case series of critically ill patients with laboratory-confirmed COVID-19 admitted to ICUs in Lombardy, Italy, the majority were older men, a large proportion required mechanical ventilation and high levels of PEEP, and ICU mortality was 26%.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Critical Care/statistics & numerical data , Hospital Mortality , Intensive Care Units/statistics & numerical data , Pneumonia, Viral/epidemiology , Positive-Pressure Respiration/statistics & numerical data , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , COVID-19 , Comorbidity , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Critical Illness/therapy , Female , Hospitalization , Humans , Italy/epidemiology , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Respiration, Artificial , Retrospective Studies , SARS-CoV-2 , Sex Distribution , Young Adult
8.
Ghana Med J ; 54(4 Suppl): 97-99, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1436200

ABSTRACT

Computed Tomography (CT) scan of the chest plays an important role in the diagnosis and management of Coronavirus disease 2019 (COVID-19), the disease caused by the novel coronavirus SARS-CoV-2. COVID-19 pneumonia shows typical CT Scan features which can aid diagnoses and therefore help in the early detection and isolation of infected patients. CT scanners are readily available in many parts of Ghana. It is able to show findings typical for COVID-19 infection of the chest, even in instances where Reverse Transcription Polymerase Chain Reaction (RTPCR) misses the diagnosis. Little is known about the diagnostic potential of chest CT scan and COVID-19 among physicians even though CT scan offers a high diagnostic accuracy.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnostic imaging , Lung/diagnostic imaging , Symptom Assessment/methods , Tomography, X-Ray Computed , Adult , Aged , COVID-19 Nucleic Acid Testing/statistics & numerical data , COVID-19 Testing/statistics & numerical data , Early Diagnosis , Female , Ghana , Humans , Lung/virology , Male , Middle Aged , Reproducibility of Results , SARS-CoV-2 , Sensitivity and Specificity
9.
Sci Rep ; 10(1): 14186, 2020 08 25.
Article in English | MEDLINE | ID: covidwho-1434143

ABSTRACT

Infections cause varying degrees of haemostatic dysfunction which can be detected by clot waveform analysis (CWA), a global haemostatic marker. CWA has been shown to predict poor outcomes in severe infections with disseminated intravascular coagulopathy. The effect of less severe bacterial and viral infections on CWA has not been established. We hypothesized that different infections influence CWA distinctively. Patients admitted with bacterial infections, dengue and upper respiratory tract viral infections were recruited if they had an activated partial thromboplastin time (aPTT) measured on admission. APTT-based CWA was performed on Sysmex CS2100i automated analyser using Dade Actin FSL reagent. CWA parameters [(maximum velocity (min1), maximum acceleration (min2) and maximum deceleration (max2)] were compared against control patients. Infected patients (n = 101) had longer aPTT than controls (n = 112) (34.37 ± 7.72 s vs 27.80 ± 1.59 s, p < 0.001), with the mean (± SD) aPTT longest in dengue infection (n = 36) (37.99 ± 7.93 s), followed by bacterial infection (n = 52) (33.96 ± 7.33 s) and respiratory viral infection (n = 13) (29.98 ± 3.92 s). Compared to controls (min1; min2; max2) (5.53 ± 1.16%/s; 0.89 ± 0.19%/s2; 0.74 ± 0.16%/s2), bacterial infection has higher CWA results (6.92 ± 1.60%/s; 1.04 ± 0.28%/s2; 0.82 ± 0.24%/s2, all p < 0.05); dengue infection has significantly lower CWA values (3.93 ± 1.32%/s; 0.57 ± 0.17%/s2; 0.43 ± 0.14%/s2, all p < 0.001) whilst respiratory virus infection has similar results (6.19 ± 1.32%/s; 0.95 ± 0.21%/s2; 0.73 ± 0.18%/s2, all p > 0.05). CWA parameters demonstrated positive correlation with C-reactive protein levels (min1: r = 0.54, min2: r = 0.44, max2: r = 0.34; all p < 0.01). Different infections affect CWA distinctively. CWA could provide information on the haemostatic milieu triggered by infection and further studies are needed to better define its application in this area.


Subject(s)
Bacterial Infections/blood , Hemostasis , Partial Thromboplastin Time/methods , Virus Diseases/blood , Aged , Aged, 80 and over , C-Reactive Protein/analysis , Dengue/blood , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/etiology , Elective Surgical Procedures , Female , Humans , Male , Middle Aged , Procalcitonin/blood , Respiratory Tract Infections/blood
10.
Res Sq ; 2020 May 12.
Article in English | MEDLINE | ID: covidwho-1431216

ABSTRACT

Background: COVID-19 is caused by the severe acute respiratory syndrome virus SARS-CoV-2. It is widely recognized as a respiratory pathogen, but neurologic complications can be the presenting manifestation in a subset of infected patients. Case presentation: We describe a 78-year old immunocompromised woman who presented with altered mental status after witnessed seizure-like activity at home. She was found to have SARS-CoV-2 infection and associated neuroinflammation. In this case, we undertake the first detailed analysis of cerebrospinal fluid (CSF) cytokines during COVID-19 infection and find a unique pattern of inflammation in CSF, but no evidence of viral neuroinvasion. Conclusion: Our findings suggest that neurologic symptoms such as encephalopathy and seizures may be the initial presentation of COVID-19. Central nervous system inflammation may associate with neurologic manifestations of disease.

11.
J Bone Joint Surg Am ; 102(12): e58, 2020 06 17.
Article in English | MEDLINE | ID: covidwho-1409847

ABSTRACT

BACKGROUND: From February 20 to April 2020, the coronavirus SARS (severe acute respiratory syndrome)-CoV-2 spread in northern Italy, drastically challenging the care capacities of the national health care system. Unprepared for this emergency, hospitals have quickly reformulated paths of assistance in an effort to guarantee treatment for infected patients. Orthopaedic departments have been focused on elderly traumatology, especially the treatment of femoral neck fractures in patients with coronavirus disease-2019 (COVID-19). The purpose of the present study was to evaluate the orthopaedic management strategy for femoral fragility fractures in COVID-19-positive patients with the hypothesis that operative treatment may contribute to the overall stability of the patient. METHODS: Sixteen patients affected by proximal femoral fracture and a recent history of fever, shortness of breath, and desaturation were admitted to the emergency room. Thoracic computed tomography (CT) and oropharyngeal swabs confirmed that they were positive for COVID-19, requiring hospitalization and prophylaxis with low-molecular-weight heparin. RESULTS: Three patients died before surgery because of severe respiratory insufficiency and multiple-organ-failure syndrome. Ten patients underwent surgery on the day after admission, whereas 3 patients had suspended their use of direct thrombin inhibitors and needed surgery to be delayed until the third day after admission. In all patients except 1, we noted an improvement in terms of O2 saturation and assisted respiration. In 9 patients, hemodynamic and respiratory stability was observed at an average of 7 days postoperatively. Four patients who underwent surgical treatment died of respiratory failure on the first day after surgery (1 patient), the third day after surgery (2 patients), or the seventh day after surgery (1 patient). CONCLUSIONS: We noted a stabilization of respiratory parameters in 12 COVID-19-positive patients who underwent surgery treatment of proximal femoral fractures. We believe that in elderly patients with COVID-19 who have proximal femoral fractures, surgery may contribute to the overall stability of the patient, seated mobilization, improvement in physiological ventilation, and general patient comfort in bed. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Betacoronavirus , Coronavirus Infections/epidemiology , Femoral Fractures/surgery , Fracture Fixation, Intramedullary/adverse effects , Frailty/complications , Pneumonia, Viral/epidemiology , Aged , Aged, 80 and over , COVID-19 , Disease Outbreaks , Female , Femoral Fractures/mortality , Femoral Fractures/virology , Frailty/mortality , Hospitalization , Humans , Italy , Male , Pandemics , SARS-CoV-2
14.
Ir J Med Sci ; 2021 May 07.
Article in English | MEDLINE | ID: covidwho-1384596

ABSTRACT

BACKGROUND: Although the lung is seen as the main target organ affected by SARS-CoV-2, other organs are also damaged. AIM: We aimed to determine the extrapulmonary findings of autopsies performed on cases with positive results with postmortem polymerase chain reaction test. METHODS: Pathological changes in extrapulmonary organs were examined with light microscopy. RESULTS: Heart, liver, spleen, kidney, pancreas, and central nervous system samples of these cases were evaluated. About 80% of the cases were men, and 20% were women. In the examination of heart, 28 of the cases had scar, 14 had acute myocardial infarction, 6 had acute and previous myocardial infarction findings, 2 had myocarditis, and 4 had interstitial mononuclear inflammatory cell infiltration. In the examination of the liver, portal inflammation was observed in 84 of the cases, steatosis in 54, centrilobular necrosis in 9, and capillary endotheliitis in the portal area in 7 of them. In the evaluation of the kidney, 37 cases had chronic pyelonephritis, 36 had tubular damage, 15 had tubulointerstitial necrosis, 16 had subcapsular microhemorrhage, 10 had capillary endothelitis, and 9 had a microvascular fibrin trombosis in their glomerular capillaries. In the central nervous system, 8 cases had infarction and liquefaction, 56 had perivascular petechial hemorrhage, 54 had acute hypoxic ischemic change, 3 had parenchymal microhemorrhage, and 52 had capillary endotheliitis. CONCLUSION: Autopsies play an important role in systematically examining the damage caused by the virus in all organs in order to elucidate the pathogenesis of SARS-CoV-2 infection and contribute to the clinical management of infected patients.

16.
Childs Nerv Syst ; 37(7): 2305-2312, 2021 07.
Article in English | MEDLINE | ID: covidwho-1384405

ABSTRACT

PURPOSE: To describe the temporal association of specific acute neurological symptoms in pediatric patients with confirmed SARS-CoV-2 infection between May and August 2020. METHODS: We performed a recollection of all the clinical and laboratory data of patients having acute neurological symptoms temporally associated with SARS-CoV-2 infection at a third-level referral hospital in Mexico City (Instituto Nacional de Pediatría). Patients in an age group of 0-17 years with acute neurological signs (including ascending weakness with areflexia, diminished visual acuity, encephalopathy, ataxia, stroke, or weakness with plasma creatinine kinase (CK) elevation) were evaluated. RESULTS: Out of 23 patients with neurological manifestations, 10 (43%) had a confirmed SARS-CoV-2 infection. Among the infected patients, 5 (50%) were males aged 2-16 years old (median age 11.8 years old). Four (40%) patients confirmed a close contact with a relative positive for SARS-CoV-2, while 6 (60%) cases had a history of SARS-CoV-2-related symptoms over the previous 2 weeks. The following diagnoses were established: 3 cases of GBS, 2 of ON, 2 of AIS, one of myositis with rhabdomyolysis, one ACA, and one of anti-NMDA-R encephalitis. CONCLUSIONS: Neurological manifestations temporally associated with SARS-CoV-2 infection were noticed in the pediatric population even without respiratory symptoms. In this study, 2 of 6 symptomatic patients had mild respiratory symptoms and 4 had unspecific symptoms. During this pandemic, SARS-CoV-2 infection should be considered as etiology in patients with acute neurological symptoms, with or without previous respiratory manifestations, particularly in teenagers.


Subject(s)
COVID-19 , Stroke , Adolescent , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Male , Mexico/epidemiology , Pandemics , SARS-CoV-2
17.
Exp Ther Med ; 21(3): 279, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1389588

ABSTRACT

As it spread globally, the new SARS-CoV-2 virus was first confirmed in Romania in February 2020, inevitably infecting individuals with diabetes mellitus (DM) along the way. Diabetes is known to affect the response of the body to pathogens and, according to studies conducted in the last 3 months, it appears that diabetic patients are at a higher risk for developing severe forms of the disease and multiple complications. We performed a retrospective study in order to assess the patients with SARS-CoV-2 infection and DM admitted to 'Sf. Parascheva' Clinical Hospital of Infectious Diseases from March 4th until June 30th, 2020. Of the total 1,080 patients admitted during this period, 85 patients (7.87%) had underlying DM, mostly type 2 (82 cases, 96.46%); the mean age of these patients was 62, and 42 were men (49.41%). Chest CTs revealed indicative SARS-CoV-2 images for all patients and their treatment included individually tailored administration of hydroxychloroquine/lopinavir + ritonavir/enoxaparin sodium/tocilizumab/antibiotherapy according to the then national and international guidelines. In total, 70 patients (82.35%) were cured and 15 succumbed to MODS and/or associated neoplasia, bringing the fatality rate to 17.64%. Although advanced age and DM have been associated with aggravated forms of SARS-CoV-2 infection, over 80% of the patients included in the present study were cured. Nonetheless, diabetes appears to be a significant predictor of morbidity and mortality in the SARS-CoV-2 infection.

18.
Viruses ; 13(4)2021 04 03.
Article in English | MEDLINE | ID: covidwho-1389536

ABSTRACT

Replication of RNA viruses is characterized by exploration of sequence space which facilitates their adaptation to changing environments. It is generally accepted that such exploration takes place mainly in response to positive selection, and that further diversification is boosted by modifications of virus population size, particularly bottleneck events. Our recent results with hepatitis C virus (HCV) have shown that the expansion in sequence space of a viral clone continues despite prolonged replication in a stable cell culture environment. Diagnosis of the expansion was based on the quantification of diversity indices, the occurrence of intra-population mutational waves (variations in mutant frequencies), and greater individual residue variations in mutant spectra than those anticipated from sequence alignments in data banks. In the present report, we review our previous results, and show additionally that mutational waves in amplicons from the NS5A-NS5B-coding region are equally prominent during HCV passage in the absence or presence of the mutagenic nucleotide analogues favipiravir or ribavirin. In addition, by extending our previous analysis to amplicons of the NS3- and NS5A-coding region, we provide further evidence of the incongruence between amino acid conservation scores in mutant spectra from infected patients and in the Los Alamos National Laboratory HCV data banks. We hypothesize that these observations have as a common origin a permanent state of HCV population disequilibrium even upon extensive viral replication in the absence of external selective constraints or changes in population size. Such a persistent disequilibrium-revealed by the changing composition of the mutant spectrum-may facilitate finding alternative mutational pathways for HCV antiviral resistance. The possible significance of our model for other genetically variable viruses is discussed.


Subject(s)
Hepacivirus/genetics , Hepacivirus/physiology , Hepatitis C/virology , Antiviral Agents/pharmacology , COVID-19 , Cell Line , Drug Resistance, Viral/drug effects , Hepacivirus/drug effects , Humans , Mutation , RNA, Viral , Ribavirin/pharmacology , Sequence Analysis , Viral Nonstructural Proteins/genetics , Virus Replication/drug effects
19.
Int J Environ Res Public Health ; 18(6)2021 03 17.
Article in English | MEDLINE | ID: covidwho-1389362

ABSTRACT

There is growing literature about the SARS-CoV-2 pathogenetic effects exerted during pregnancy and whether vertical transmission or premature birth is possible. It is not well known whether changes in the immune system of pregnant women may lead to a marked susceptibility to infectious processes and the risk of adverse maternal and neonatal complications such as preterm birth, spontaneous abortion, hospitalization in an intensive care unit, transmission to the fetus or newborns, and fetal mortality are poorly understood. Along with this ongoing debate, it is not well defined whether, during pregnancy, the role of host susceptibility in producing a specific inflammatory response to SARS-CoV-2 may represent distinctive markers of risk of vertical transmission. Furthermore, SARS-CoV-2 impact on the vaginal microbiome has not yet been described, despite mounting evidence on its possible effect on the gastrointestinal microbiome and its influence on infectious diseases and preterm labor. This report describes the impact of SARS-CoV-2 on a twin pregnancy diagnosed with infection at the third trimester of gestation including tissue infections, inflammatory response, antibody production, cytokine concentration, and vaginal microbiome composition. We identified a pattern of cytokines including IL1-Ra, IL-9 G-CSF, IL-12, and IL-8 differently expressed, already associated with previously infected patients. We detected a similar concentration of almost all the cytokines tested in both twins, suggesting that the SARS-CoV-2-induced cytokine storm is not substantially impaired during the placental passage. The analysis of the vaginal microbiome did not show relevant signs of dysbiosis, similar to other healthy pregnant women and twin healthy pregnancies. The aim of this report was to analyze the immunological response against SARS-CoV-2 infection and virus tissue tropism in a twin pregnancy.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Premature Birth , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Pregnancy , Pregnancy Outcome , Pregnancy, Twin , SARS-CoV-2
20.
Front Immunol ; 12: 660019, 2021.
Article in English | MEDLINE | ID: covidwho-1389181

ABSTRACT

SARS-CoV-2 is the cause of a recent pandemic that has led to more than 3 million deaths worldwide. Most individuals are asymptomatic or display mild symptoms, which raises an inherent question as to how does the immune response differs from patients manifesting severe disease? During the initial phase of infection, dysregulated effector immune cells such as neutrophils, macrophages, monocytes, megakaryocytes, basophils, eosinophils, erythroid progenitor cells, and Th17 cells can alter the trajectory of an infected patient to severe disease. On the other hand, properly functioning CD4+, CD8+ cells, NK cells, and DCs reduce the disease severity. Detailed understanding of the immune response of convalescent individuals transitioning from the effector phase to the immunogenic memory phase can provide vital clues to understanding essential variables to assess vaccine-induced protection. Although neutralizing antibodies can wane over time, long-lasting B and T memory cells can persist in recovered individuals. The natural immunological memory captures the diverse repertoire of SARS-CoV-2 epitopes after natural infection whereas, currently approved vaccines are based on a single epitope, spike protein. It is essential to understand the nature of the immune response to natural infection to better identify 'correlates of protection' against this disease. This article discusses recent findings regarding immune response against natural infection to SARS-CoV-2 and the nature of immunogenic memory. More precise knowledge of the acute phase of immune response and its transition to immunological memory will contribute to the future design of vaccines and the identification of variables essential to maintain immune protection across diverse populations.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/physiology , Animals , Antibodies, Neutralizing/metabolism , Antibodies, Viral/metabolism , Disease Resistance , Epitopes, T-Lymphocyte/immunology , Humans , Immunity, Cellular , Immunologic Memory
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